Several diseases are thought to be caused by the abnormal folding and aggregation of disease-specific proteins. These proteins can accumulate into pathologically diagnostic accumulations, known as amyloids, which are visualized by certain histologic stains. Amyloids are thought to elicit inflammatory responses and have multiple negative consequences for the involved tissues. In addition, smaller aggregates of abnormally folded protein may exist and exert cytotoxic effects.
Type-2 diabetes (T2D) is a common disease where amyloid accumulations are often seen in the pancreas. The amyloid accumulations include islet-amyloid polypeptide (IAPP), also known as amylin. Accumulating evidence associates toxic IAPP oligomers and IAPP deposits with T2D. See, e.g., Haataja et al. (2008), Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis, Endocrine Reviews 29:303-316. For example, there is evidence of the involvement of toxic IAPP oligomers in p-cell apoptosis in T2D. See Janson et al. (1999), The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles, Diabetes 48:491-498; Lorenzo et al. (1994), Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus, Nature 368:756-760; Ritzel & Butler (2003), Replication increases beta-cell vulnerability to human islet amyloid polypeptide-induced apoptosis, Diabetes 52:1701-1708. In addition, humans, monkeys and cats express an amyloidogenic toxic form of IAPP and develop diabetes characterized by islet amyloid deposits. See O'Brien et al. (1993), Islet amyloid polypeptide: A review of its biology and potential roles in the pathogenesis of diabetes mellitus, Vet. Pathol. 30:317-332. IAPP deposits are also found in insulinomas. See O'Brien et al. (1994), Islet amyloid polypeptide in human insulinomas. Evidence for intracellular amyloidogenesis, Diabetes 43: 329-336.
Pre-diabetes is a condition in which individuals have blood glucose levels higher than normal but not high enough to be classified as diabetes. People with pre-diabetes have an increased risk of developing T2D. People with pre-diabetes have impaired fasting glucose (“IFG”) or impaired glucose tolerance (“IGT”), and some people have both IFG and IGT (National Diabetes Statistics, 2007).